Absorption, Metabolism, and Excretion of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease

The Pharmacokinetic Profile of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease

The objective of this study is to evaluate the pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite following administration of a single 1500 mg dose of Ferriprox in patients with sickle cell disease.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: single 1500 mg dose of Ferriprox

Detailed Description

This is a single-arm, single-dose study of Ferriprox in patients with sickle cell disease. Patients found to be eligible will visit the clinic the day before receiving the drug, in order to reconfirm eligibility and to undergo baseline assessments, and will receive a single dose of 1500 mg Ferriprox under fasting conditions. Blood and urine samples for pharmacokinetic assessment will be collected over a 10-hour period. Standard safety assessments will be performed throughout the study, and patients will return for a safety follow-up.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM-Hopital Notre-Dame

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 18-45 years of age (inclusive)
2. Diagnosis of sickle cell disease, confirmed by Hb electrophoresis
3. Body weight ≥ 50 kg
4. Body mass index (BMI) ≥ 18 and ≤ 32 kg/m^2
5. Absolute neutrophil count (ANC) of >1.5 x 10^9/L
6. Women of childbearing potential must agree to either be sexually inactive or use an acceptable method of birth control for 14 days prior to dosing and for 30 days afterwards
7. A fertile heterosexual male must agree that he or his partner will use an effective method of contraception for 14 days prior to dosing and for 30 days afterwards

Exclusion Criteria:

1. History or presence of hypersensitivity or idiosyncratic reaction to Ferriprox
2. Use of Ferriprox within the past 3 months
3. History of malignancy
4. Evidence of abnormal liver function (serum Alanine Transaminase (ALT)level > 5 times upper limit of normal or creatinine levels >2 times upper limit of normal)
5. A serious, unstable illness, as judged by the Investigator, within the past 3 months before screening visit including but not limited to hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease
6. Hemodialysis during the week prior to dosing or planned for the day of dosing
7. Known difficulty in providing blood samples
8. Disorders or surgery of the gastrointestinal tract that may interfere with drug absorption or may otherwise influence the Pharmacokinetic (PK) results (e.g., resection of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.)
9. Clinically significant abnormalities on 12-lead ECG (e.g., QT interval corrected using Fridericia's formula (QTcF) ≥ 430 ms in males or ≥ 450 ms in females)
10. Use of tobacco/nicotine-containing products for at least 3 months prior to study drug administration
11. Use of any drugs within the past 14 days that are metabolized by the Uridine diphosphate glucosyltransferase enzyme (UGT1A6) and hence could affect the PK of Ferriprox
12. Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug (whichever is longer) prior to study drug administration
13. Pregnant or nursing female

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Ferriprox; single 1500 mg dose of Ferriprox	Drug: single 1500 mg dose of Ferriprox; A single dose of 1500mg of Ferriprox (three 500mg tablets) administered under fasting conditions; Other Names: deferiprone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	Cmax (maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.	10-hour interval
Tmax for Deferiprone and Deferiprone 3-O-glucuronide	Tmax (time to the maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).	10-hour interval
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide	AUC0-∞ (area under the curve, zero to infinity) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.	10-hour interval
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide	T1/2 (apparent terminal elimination half-life) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.	10-hour interval

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of Adverse Events	From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up)
Frequency of Serious Adverse Events	From Day 1 (Dosing) to Day 30 post-dose

Collaborators and Investigators

• Sponsor: ApoPharma
• Investigators: Principal Investigator: Denis Soulieres, MD, CHUM - Hopital Notre-Dame

Publications and helpful links

General Publications

• Soulieres D, Mercier-Ross J, Fradette C, Rozova A, Tsang YC, Tricta F. The pharmacokinetic and safety profile of single-dose deferiprone in subjects with sickle cell disease. Ann Hematol. 2022 Mar;101(3):533-539. doi: 10.1007/s00277-021-04728-0. Epub 2022 Jan 4.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: April 11, 2013
• First Submitted That Met QC Criteria: April 16, 2013
• First Posted (ESTIMATE): April 19, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics; iron overload; sickle cell disease; Ferriprox; deferiprone
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: LA41-0412